CBCL 4 Flashcards
Many patients with colon cancer develop anemia. Which of the following is correct?
This represents a direct effect of the tumor due to blood loss into the GI tract
This represents a manifestation of cancer cachexia
This represents a paraneoplastic syndrome
This represents poor dietary habits of most patients with colon cancer
This represents the fact that many elderly patients are anemia and colon cancer is more common in elderly patients
This represents a direct effect of the tumor due to blood loss into the GI tract.
Most colon cancers are associated with blood loss into the GI tract. The iron content of this blood loss cannot be recovered; therefore iron deficiency develops. In the US, iron deficiency in adults is due to chronic blood loss until proven otherwise.
An example of a paraneoplastic syndrome associated with squamous cell carcinoma of the lung is?
- Hemoptysis leading to anemia
- Hypercalcemia
- Pleural effusion
- Post-obstructive pneumonia
- Cough
A paraneoplastic syndrome refers to a pattern of symptoms or symptom complexes associated with cancer that cannot be directly explained by local or distant spread of the cancer or by the elaboration of hormones indigenous to the tissue from which the tumor arose. Hypercalcemia associated with squamous cell carcinoma of the lung is a paraneoplastic syndrome. It is caused by elaboration of a PTH-like peptide by tumor cells; normal lung cells do not express PTH or PTH-like peptide. Hemoptysis, pleural effusion, post-obstructive pneumonia, and cough are all directly related to the cancer and its local spread.
What is this?
Atypical mitotic figures are characteristic of?
Malignant neoplasm
A mutation in what gene is most commonly associated with Familal adenomatous polyposis (FAP)?
APC gene mutations
What is this?
Thyroid adenoma
The molecular pathology lab receives a tumor specimen that shows a mutation in BRAF (V600E). What is the most likely diagnosis?
Cannot be determined
Activating BRAF mutations like V600E can be seen in many different tumors. The mutation cannot determine the type of tumor, but can help in classification in association with histologic findings. BRAF inhibitors can be used therapeutically based on the presence of this mutation.
What are the Amsterdam guidelines for Lynch Syndrome?
The 3-2-1
3 - Family members
2 - successive generations
1 - under the age of 50
A 25-year-old woman has an extensive family history of cancer including breast cancer, osteosarcoma, and brain tumors on her mother’s side. Most tumors occurred before age 50. You suspect Li-Fraumeni syndrome. Li-Fraumeni syndrome is associated with inherited mutations of which of the following genes?
Li-Fraumeni syndrome is associated with inherited mutations of TP53.
A 77-year-old man presents with metastatic colon cancer. Since many colon cancers have activating mutations of epidermal growth factor receptor (EGFR) you would like to use an EGFR inhibitor for treatment. Activating mutations in which of the following genes will affect your treatment decision?
- ABL
- Bcl-2
- KRAS
- RB
- TP53
Activating KRAS mutations will render anti-EGFR treatment ineffective since KRAS is downstream from EGFR.
A 73-year-old woman presented with a pathologic fracture of her left femoral shaft. Tissue removed at the time of internal fixation was submitted for pathologic examination and is shown in the image. An immunohistochemical stain for cytokeratin is shown in the inset. Which of the following is the most likely diagnosis?
Metastatic Carcinoma - The neoplastic cells stain positively for an immunohistochemical stain for cytokeratin, demonstrating epithelial origin of the neoplasm. The neoplasm is malignant, based on the infiltrative growth pattern and lack of significant differentiation. A malignant epithelial neoplasm is called carcinoma. Melanoma is a malignant neoplasm derived from melanocytes (would be negative for cytokeratin). Lymphoma and leukemia are malignant neoplasms derived from hematopoietic cells (would be negative for cytokeratin). The image does not show normal hematopoietic elements.
Two patients with colon cancer have the following findings:
Pt 1 - Well differentiated adenocarcinoma, T3N1M0
Pt 2 - Poorly differentiated adenocarcinoma, T1N0M0
Which of the following is correct?
- Patient 1 has a better prognosis since the tumor is well differentiated
- Patient 1 has a worse prognosis since the stage is higher
- Patient 1 has evidence of liver metastasis
- Patient 2 has a more locally advanced cancer
- Patient 2 has evidence of lymph node metastasis
Patient 1 has a worse prognosis since the stage is higher. Staging has a much greater impact on prognosis than grading.
Which gene is implicated in the development of familial adenomatous polyposis?
APC
Which of the following pathologic features is most likely to be associated with abnormal tissue associated with a benign neoplasm?
Answers:
- Atypical mitotic figures
- Infiltration of surrounding tissue
- Encapsulation
- Poor differentiation
- Anaplasia
Encapsulation is often a feature of benign neoplasms. Atypical mitotic figures, infiltration of surrounding tissue, poor differentiation, and anaplasia are characteristics of malignant neoplasms
Is the use of CEA good for diagnostic and screening purposes?
Though it is a tumor marker it has low diagnostic ability to detect primary colorectal cancer due to significant overlap with benign disease and low sensitivity for early-stage disease. The sensitivity of CEA for CRC was only 46%. The specificity of the test was 89% . Non-cancer-related causes of an elevated CEA include gastritis, peptic ulcer disease, diverticulitis, liver disease, chronic obstructive pulmonary disease, diabetes, and any acute or chronic inflammatory state. It is not recommended to use CEA as a diagnostic or screening test.
What is this in the colon?
Colonic Adenoma
What is this?
Mixed tumor of the parotid - who knew :P
Inherited mutations in which of the following genes is likely to be associated with a hereditary cancer syndrome?
APC - Inherited cancer syndromes are most often due to inherited mutations of tumor suppressor genes and DNA repair genes.
A 72-year-old man presents with colon cancer with liver metastasis. You are considering using Bevacizumab (VEGF inhibitor) as part of treatment. You are explaining this to the patient. Which of the following is correct?
Bevacizumab will cure his cancer
Bevacizumab will have no side effects
Bevacizumab will kill all tumor cells in the colon, but not the liver
Bevacizumab will kill all tumor cells in the liver, but not the colon
Bevacizumab will shrink the tumor but will not eliminate it
Bevacizumab will shrink the tumor but will not eliminate it
VEGF inhibitors can shrink the tumor but do not eliminate all cancer cells; hence are not curative. Significant side effects exist.
If a pt develops colorectal cancer at the age of 72, should the patient be worried about an inherited aspect of the disease?
No, most inherited colon cancers will manifest themselves much earlier
A specimen of colon cancer tissue is submitted for microsatellite instability (MSI) testing and is positive for MSI (MSI-high). Which of the following is most likely true?
- This cancer has worse prognosis than a stage matched cancer without MSI
- This cancer is never associated with occult blood in the stool
- This cancer is on the right side of the colon
- This cancer is unable to metastasize
- This cancer shows complete and normal expression of all mismatch repair proteins
This cancer is on the right side of the colon
Colon cancers with MSI are more often on the right side of the colon. MSI is a marker for loss of one or more mismatch repair genes.
Epigenetic carcinogens do what?
Do not damage DNA
What are the characteristics of normal colon tissue?
Gland forming epithelium with numerous goblet cells
Goblet cells have mucous containing vacuoles that take up most of cell
Glands are uniformly distributed and nuclei are arranged in single layer at base of the cells in the glands
What pathologic process is represented in the colonic adenoma removed from this patient?
Colonic adenoma is a manifestation of epithelial dysplasia.
A 32-year old woman gives birth to a stillborn infant with anencephaly, renal cysts and polydactyly. Following a request to sequence their baby’s DNA, the parents learn their baby was afflicted with Meckel Gruber’s Syndrome. Which cellular process was not disrupted in their baby before her demise?
Primary cilia mediate signaling pathways, which regulate transcription and proliferation. Since the basal body of primary cilia is comprised of the mother centriole, primary cilia affect mitosis and cell cycle progression. Primary cilia do not have a role in translation. Proteins must be translated in the cytoplasm and transported to the cilium.
What is the mechanism by which APC mutations leads to FAP?
APC is the key regulator of B-catenin The APC protein normally binds to and promotes degradation of β-catenin. With loss of APC function, β-catenin accumulates and translocates to the nucleus, where it forms a complex with the DNA-binding factor TCF and activates the transcription of genes, including MYC and cyclin D1, that promote proliferation.
Primary cilia do not have a role in what?
Translation
What is this tissue and what is wrong?
Nothing is wrong! This is normal colon tissue.
Are mutations in MSH characteristic of sporadic cancers?
NO
What is the inheritance pattern of Lynch syndrome?
Autosomal dominant
What is this in the colon?
First off…. it isn’t great. This is a colonic adenocarcinoma. Look at all the blue!!!
A subcutaneous mass was removed from the inguinal region of a 52-year-old male and is shown in the accompanying image. The tissue is best described as a(n)?
Identification of malignancy and distinguishing a lipoma from a liposarcoma: there are mesenchymally-derived cells throughout the liposarcoma.
A 72 year old man presents with lower GI bleed and colonoscopy shows an ascending colon tumor. The tumor is resected and determined to be an adenocarcinoma. Immunohistochemical staining shows loss of MLH1 in the tumor cells. The patient has no family history of colon cancer or any other cancer. An activating BRAF mutation is present. What is the most likely mechanism of loss of MLH1 in this patient?
Patients with microsatellite instability and loss of MLH1 with activating BRAF mutations usually have reduced expression of MLH1 due to methylation of the MLH1 promotor.
Which of the following genes is commonly implicated in sporadic colorectal cancer?
- MSH
- Rb
- VHL
- APC
- NF1
Mutations in APC are often seen in sporadic colorectal cancer. Mutations in Rb are associated with retinoblastoma. Mutations in MSH may be associated with hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome but are not usual in sporadic colorectal cancer. Rb, VHL, and NF1 genes are not associated with colorectal cancer.
A 66-year-old man presents with new onset seizures. A CT scan shows a 3.5 cm mass in the brain and a biopsy is performed. The tumor cells are positive for cytokeratin by immunohistochemistry. The most likely diagnosis is?
The section gland formation. The presence of cytokeratin positivity indicates epithelial origin, hence metastatic carcinoma.
What is this?
Leiomyoma - but it really just looks like smooth muscle
A 6.5 cm retroperitoneal tumor is removed from a 65-year-old man. A representative image is shown below. Immunohistochemical staining shows the tumor cells to be positive for vimentin and negative for cytokeratin. An oil red O stain shows that the cytoplasmic vacuoles in the tumor cells contain lipid. This most likely represents?
Liposarcoma
The tumor is likely of mesenchymal origin since it is positive for vimentin and negative for cytokeratin. The presence of lipid in the cells is indicative of origin from adipocytes; hence this is most likely Liposarcoma.
What is this?
Lipoma - low cellularity, minimal nuclear atypia, resemblance to normal fat
A 55 year old man undergoes routine screening colonoscopy and a polyp is removed. As compared to normal colonic tissue, which of the following histologic features support that this is an adenoma?
Stratified nuclei - Adenoma is characterized by a more deeply basophilic appearance due to increased nuclear density, nuclear enlargement, nuclear hyperchromasia, nuclear stratification, and loss of mucin.
What is the important aspect of this picture? Benign or malignant?
Atypical mitotic body - characteristic of a malignancy
A 13-year-old girl has a large tumor of the right knee. A biopsy is performed and histologic examination shows large atypical cells with interspersed pink material consistent with osteoid. What is the most likely diagnosis?
The presence of osteoid is indicative of bone forming property of the tumor, hence osteosarcoma.
